This is an application for a K23 award for Dr. Heidi Schambra, a neurologist at Columbia University. Dr. Schambra's long-term career goals are to become a leading clinical investigator in stroke recovery, to improve the well-being of patients with neurologic injury, and to advance the field of neurorehabilitation. This K23 award will provide her with the support necessary to accomplish her short-term career goals, which are: (1) to conduct prospective clinical research in stroke patients; (2) to become expert in quantitative motor recovery and ad- vanced stroke neurophysiology; (3) to implement biostatistician methodology in clinical research; and (4) to de- velop an independent clinical research career that is R01-funded. To achieve these goals, Dr. Schambra has assembled a mentoring team comprised of a primary mentor, Dr. John Krakauer, an internationally recognized authority in motor learning and stroke recovery, and two co-mentors: Dr. Randolph Marshall, a leader in pros- pective clinical research in stroke; and Dr. Pietro Mazzoni, an expert in motor control in neurologically impaired patients. She will also have three scientific advisors: Dr. Pablo Celnik, an authority in stroke neurophysiology; Dr. Todd Ogden, a biostatistician with extensive biomedical research experience; and Dr. Robert Sainburg, a specialist in motor control in stroke. Dr. Schambra has the firm institutional support of the Departments of Neu- urology and Rehabilitation Medicine, and she will receive comprehensive instruction from Columbia's robust scientific and clinical communities. There is a fundamental gap in our mechanistic understanding of motor recovery after stroke. The long- term objective is to use knowledge about biological recovery processes to develop mechanism-based treat- ments for patients after stroke. The specific objective here is to determine how longitudinal changes in corti- cospinal and intracortical physiology relate to changes in motor impairment in either limb after stroke. The ra- tionale for this project is that its successful completion would strongly suggest a mechanistic role for neurophy- siology in motor recovery. This project will leverage the existing infrastructure of a multicenter parent study, lead by Dr. Krakauer, to evaluate 45 stroke patients over 5 time points in the first year following stroke. Dr. Schambra will test the central hypothesi that certain stereotyped recovery behaviors will have distinct neuro- physiological signatures. She will do this by identifying the neurophysiologic correlates of: the recovery of strength and motor control in the paretic arm (Aim 1), the proximal-to-distal progression of motor recovery in the paretic arm (Aim 2), and the recovery of motor control in the nonparetic arm (Aim 3). All aims will utilize correlation analyses. The proposed research is innovative in its use of quantitative physiologic and behavioral measures to study a surprisingly neglected period after stroke. It is expected to be significant by providing a rational basis for targeting specific neurophysiologic components at different times after stroke, to be proposed by Dr. Schambra in a future R01 application. PUBLIC HEALTH RELEVANCE: The proposed research will improve our understanding of the brain physiology that relates to recovery after stroke. It is relevant to public health, because th knowledge gained will be used to develop better rehabilitation strategies that improve recovery, reducing the burden carried by patients with stroke.